In the US in 2001, there were about 29,000 new cases of cancer of the pancreas, and nearly that number died from it, making it the 4th most frequent cause of cancer death, after lung, breast/prostate and colorectal cancer. Over the lifetime, more than 1% of the population is affected, with blacks having a bit higher rates than whites. Survival with this cancer is dismal: one year about 20-30%, and 5-year, about 5%. Most patients present with advanced disease, and the standard treatments do not much alter the progressive, fatal course. Aside from major-gene causes underlying perhaps 5% of cases, the one known risk factor for pancreatic cancer is cigarette smoking, which doubles the risk. Studies of dietary factors have not been entirely consistent but do suggest associations of higher risk with animal product intake and lower risk with consumption of fruits or vegetables. This application describes a new hypothesis on the etiology of pancreatic cancer, and provides a substantial body of laboratory and epidemiologic evidence in support of it. To examine this hypothesis, we will conduct, in the state of CT, a population-based case-control study to examine infectious, genetic, dietary, lifestyle and medical history factors. In total, 600 pancreas-cancer cases aged 35-79 years will be identified prospectively via the ultra-rapid program of the Rapid Case Ascertainment Shared Resource at Yale. About 600 randomly selected population controls will be frequency matched to the cases by age and gender. Controls will be identified using enhanced random-digit dialing methods. All subjects will be interviewed in person by trained interviewers using a standardized, structured questionnaire that will include sections on tobacco use and medical history, a standard food frequency/supplements questionnaire, and questions about other factors specific to our hypothesis. A small blood sample will be drawn for use in testing for exposure to certain infections, and for four DNA polymorphisms relevant to our hypothesis. Average daily intake of dietary nutrients will be calculated from the diet histories, and uni- and multivariate analyses will be used to estimate relative risks for comparison of the cases with the controls. The factors to be examined here have received little attention with respect to pancreas cancer, and the proposed study will evaluate them systematically in a vigorous, large-scale and integrated project. [unreadable] [unreadable]